Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study

Abstract

Background Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. Methods HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n=100). Comparison was made with an HIV-infected, non-meningitis cohort (n=110). Results Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P=0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores<-1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P=0.002). Conclusions Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.

Cryptococcal meningitis is a cause for cross‐reactivity in cerebrospinal fluid assays for anti‐Histoplasma, anti‐Coccidioides and anti‐Blastomyces antibodies

“…Subjects were prospectively enrolled in a study at Mulago National Referral Hospital in Kampala, Uganda, with appropriate IRB approvals and the written informed consent of the subjects or their surrogates. From November 2010 until December 2013, HIV‐infected persons with CD4 <200 cells/μL suspected to have meningitis were enrolled . Cryptococcal meningitis was diagnosed by CSF cryptococcal antigen detection via latex agglutination or lateral flow assay (ImmunoMycologics) and/or fungal culture.…”

Cryptococcal Meningitis: Diagnosis and Management Update

“…In addition to high mortality, cryptococcal meningitis has substantial morbidity. Survivors can suffer from irreversible blindness and deafness, as well as reversible neurocognitive impairments (5). …”

Neurocognitive function in HIV-infected persons with asymptomatic cryptococcal antigenemia: a comparison of three prospective cohorts

“…Secondly, the repeat testing of neurocognitive function which showed improvement after 1 month of ART may have a component of improvement due to a practice effect, but overall appears quite promising for longer term function. As shown previously among cryptococcal meningitis survivors, their neurocognitive function normalizes to within one standard deviation of population norms within 1 year of ART [14]. Additionally, although meningitis was excluded in the HIV-infected control population, this population was not tested for CrAg.…”

“…On several measures of neurocognitive function, HIV-infected CrAg + persons did not differ significantly from survivors of cryptococcal meningitis who were tested at 1 month after meningitis diagnosis [14]. Secondly, longitudinal assessment of asymptomatic CrAg + persons found that they had significant improvement in neurocognitive function on most neurocognitive measures after the first 4 weeks of ART.…”